2006 Fiscal Year Final Research Report Summary
Association analysis of schizophrenomimetic- and D-serine-inducible genes in bipolar disorder and schizophrenia.
| Project/Area Number |
17591197
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Tokyo Medical and Dental Unversity |
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Principal Investigator |
ISHII Sumikazu Tokyo Medical and Dental University Medical Hospital, Psychiatry, Research Assistant, 医学部, 教務職員 (20106660)
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| Co-Investigator(Kenkyū-buntansha) |
KASHIWA Atsushi Tokyo Medical and Dental University Medical Hospital, Psychiatry, Assistant Professor, 医学部附属病院, 講師 (10301227)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Bipolar disorder / D-serine / D-serine modulator-1 gene (dsm-1) / NMDA receptor / PAPS / PAPST1 / Schizophrenia / SNP |
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| Research Abstract |
Hypofunction of the N-methyl-D-aspartate (NMDA) type glutamate receptor-mediated neurotransmission has been hypothesized to underlie the pathophysiology of schizophrenia. In the presence of glutamte, NMDA receptor activity is modulated by glycine and D-serine. In this study, we examined the association of PAPST1 (3'-Phosphoadenosine 5'-Phosphosulfate Transporter 1) in schizophrenia and bipolar disorder, (1) because PAPST1 is the human ortholog of the rat dsm-1, D-serine modulator-1, which modulate the D-serine transport, and (2) because of the suggestion of a genetic overlap between affective disorders and schizophrenia. In the case-control study, three polymorphisms, rs 575034, rs 1875324 and rs 3832441, showed a significant association with bipolar disorder (allelic associations, p=.0074, p=.0075 and p=.0451, respectively). The test of genotype frequency of the SNP (rs3832441) remained significant even after Bonferroni correction (alpha=0.0071) for multiple testing. The haplotypes constructed from these three SNPs were also associated with the bipolar disorder. However, no association was found in family-based association analysis in Caucasian bipolar disorder trios. The present study suggests that SNPs in the PAPST1 may confer the genetic risk for bipolar disorder.
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